What are the 4 nitrogenous bases that make up DNA?
Adenine and Guanine (double carbon-nitrogen rings - purines)
Cytosine and thymine (single carbon-nitrogen rings - pyrimidines)
What are the 3 basis components of DNA?
pentose sugar molecule
What is the key to accurate DNA replication?
Complementary base pairing of adenine with thymine and guanine with cytosine: A-T and G-C.
What is the function of DNA polymerase?
It travels along the single DNA strand and adds the correct nucleotides to the free end of the new strand while proofreading each strand as it goes. It essentially ensures the accuracy of DNA replication.
What is a mutation?
The inherited alteration of genetic material.
What is a mutagen?
An agent that incrases the frequency of mutations. (radiation, chemicals, etc.)
What are Mutational hot spots and give an example of a common one.
Certain areas of some chromosomes that have particularly high mutation rates. The sequence of cytosine followed by guanine (CG) is highly susceptible to mutation and accout for a large percentage of disease-causing mutations.
Where in the cell is DNA formed?
Where does protein synthesis take place?
on ribosomes in the cytoplasm
What makes up RNA?
What is the difference in makeup of RNA versus DNA?
RNA has the sugar molecule ribose rather than deoxyribose and has the base uracil rather than thymine. So it is C,A,G,U rather than C,A,G,T.
The process by which RNA is synthesized from DNA template to form mRNA.
What is translation?
The process by which RNA directs the synthesis of a polypeptide. mRNA interacts with tRNA which has a site for the attachment of amino acids (which mRNA does not have). Ribosomes bind to the mRNA then the tRNA to initiate base pairing between mRNA and tRNA. Then the amino acids can be translated into peptide bonds that will eventually be released into the cytoplasm to perform its required functions.
How many pairs of chromosomes does each cell have?
23 pairs in diploid cells.
What does homologous mean?
The autosomal pairs (22 of the 23) of chromosomes in males and females are identical in appearance (homologous). The remaining pair of chromosomes are the sex chromosomes which have 2 homologous X chromosomes in females, and a nonhomologous pair, X and Y, in males.
What is triploidy?
When there is 3 copies of each chromosome (incompatible with life)
What is aneuploidy?
A somatic cell that does not contain a multiple of 23 chromosomes as a result of nondisjunction (an error in which chromosomes fail to separate normally during meiosis or mitosis.)
What is trisomy?
A cell containing 3 copies of one chromosome. This is an example of aneuploid.
What is worse, monosomy or trisomy and why?
Monosomy is worse because the loss of chromosome material has more serious consequences than the duplication of chromosome material.
What is trisomy 21?
What is Turner syndrome?
has the karyotype 45,X. Has no Y chromosomes and is female
What is Klinefelter syndrome?`
2 X chromosomes and 1 Y chromosome (47,XXY karyotype) - male appearance, sterile, may have gynecomastia.
What is an example of chromosome deletion?
cri du chat syndrome (cry of the cat). Where broken chromosomes and loss of DNA occures without appropriate spontaneous repair.
Does chromosomal inversion cause a change in genetic material? Explain
Not for the carrier. there is no loss or gain of genetic material - only a backwards expression of the genes. Problems ony occur in the offspring of individiduals carrying the inversion. Offspring may then have chromosome deletions or duplications.
Fragile X is a mutation where on the chromosome?
The long arm of the X chromosome is broken
What is it called if someone has identical genes at a locus?
What is it called if someone has two different genes at one locus?
What is a genotype?
The genetic makeup or composition of the genes at a given locus.
What is phenotype?
the outward appearance of an individual based on their genotype.
For a recessive allele to be expressed, it must be what?
What are Mendel's two basic rules of the Chromosome Theory of Inheritance?
1) Principle of segretation: homologous genes separate from one another during reporduction and each reproductive cell carries only one of the homologous genes.
2) Principle of independent assortment: the hereditary transmission of one gene has no effect on the transmission of another.
What is autosomal dominance?
The union of one normal homozygous recessive parent and one affected heterozygous dominant parent. (Dd + dd) There is a 50% chance of passing it on to offspring. Diseases are rare because rarely do 2 affected parents mate.
What are 3 important characteristics of autosomal dominant trait?
1) 2 sexes exhibit the trait in equal proportions and are equally likely to pass on the trait to offspring.
2) No skipping of generations. If a child has a disease, one of the parents must have it also.
3) Heterozygous individuals transmit the trait to about half of their children. However, it is still possible that all or none of the children may have the trait.
Define recurrence risk?
The probability that subsequent children will have the disease.
Define germline mosaicism?
When 2 or more offspring present symptoms of an autosomal dominant disease when there is no family h/o the dz. Due to mutations that occured during embryonic development that efffected all or part of the germline but few or none of the somatic cells of the embryo.
Define penetrance and incomplete penetrance?
Penetrance: The % of individuals with a specific genotype who also exhibit the expected phenotype.
Incomplete Penetrance: the person with the gene for a dz may no exhibit the diz phenotype but still be able to transmit the dz to the next generation. (ie. retinoblastoma)
What is autosomal recessive inheritance?
When two heterozygous carriers for a dz reproduce and pass on the recessive trait to their offspring who then is homozygous affected. 25% recurrence risk.
Usually have delayed age of onset, incomplete penetrance, and variable expressivity
What are 4 important criteria for autosomal recessive inheritance?
1) males and females are affected equally
2) consanguinity is often present (inbreeding)
3) dz is seen in siblings but usually not in their parents
4) 1/4 of teh offspring of carrier parents will be affected.
________ are more frequently affected by X-linked recessive diseases.
What are the 4 important characteristics of X-linked recessive inheritance?
1) more often affects males
2) never transmitted from father to son because a father can only give a son a Y chromosome.
3) can have the appearance of "skipped generation"
4) gene is passed from an affected father to all his daughters, who, as phenotypically normal carriers, transmit it to about half their sons, who are then affected. (skipped generation affect)
Define incidence rate.
the number of NEW cases of a dz reported during a specific period divided by the number of individuals in the population.
Define prevalence rate
The proportion of the population affected by a dz at a specific poin in time.
It is determined by both the incidence rate and the length of survival period in affected individuals.
Define relative risk
incidence rate of the dz among individuals exposed to a risk factorincidence rate of the dz among individuals NOT exposed to risk factor
When traits are polygenic (effects of multiple genes) and multifactorial (effects of environmental factors), they appear with what type of curve or distribution when graphed.
Normal, bell-shaped distribution
Describe liability distribution
When a dz does not follow the bell-shaped distribution. They are either present or absent regardless of inheritance patterns expected.
What does it mean when a person is below the threshold of liability?
the person appears "normal" or has less chance of developing the dz
What does it mean to be above the threshold of liability?
The person is affected by the dz. Has more of the dz-causing genes and environmental factors.
Monozygotic twins are...
identical with the same genetic makeup
Dizygotic twins are...
fraternal with different genetic makeup much like any other siblings.
What is the difference between a concordant and discordant trait?
If both members of a twin pair share a trait (cleft palate) they are concordant traits. It they do not share the trait, they are doscordant traits.
Mucus, perspiration, saliva, tears and earwax are all examples of what type of barriers?
What are the epithelial antimicrobial glycoproteins that play a major role in protection agains respiratory infections?
Collectins produced and secreted in the lungs.
What is the epithelial antimicrobial in the intestinal epithelium that specifically reacts against gram-negative bacteria?
Bactericidal/permeability-inducing protein (BPI)
What is the epithelial antimicrobial in the intestinal epithelium that specifically reacts agains gram-positive bacteria .
What are the "cardinal signs of inflammation"?
redness, pain, swelling, heat
What are the 3 characteristic changes in the microcirculation near the site of an injury?
2) increased vascular permeability and leakage of fluid out of the vessel.
3) WBC adherence to the inner walls of vessels and their migration thru vessel walls to the site of the injury. (diapedesis)
Proteins from which plasma protein system are among the body's most potent defenders agains bacterial infection and why?
The Complement System because it can destroy pathogens directly and can activate or collaborate with every other component of the inflammatory response.
Name the 3 different cascades/pathways that can activate the complement system?
1) classical pathway: activated by the antigen-antibody immune complex. (efficient activation of this pathway requires concurrent binding of C1 to at least 2 antibody molecules)
2) Lectin pathway: activated by bacterial carbohydrates.
3) alternative pathway: activated by gram-negative bacterial and fungal cell wall polysaccharides.
What are the 4 functions of the complement system?
1) anaphylatoxic activity resulting in mast cell degranulation.
2) leukocyte chemotaxis
3) opsonization (tagging of micro-organisms for destruction or cell lysis)
4) cell lysis
What are the 4 functions of the clotting system (coagulation cascade)?
1) prevent the spread of infection to adjacent tissue
2) traps microorganisms and foreign bodies at the site of inflammation for removal by infiltrating cells (neutrophils and macrophages)
3) forms a clot to stop bleedin
4) provides a framework for future repair and healing.
What marks the end of the coagulation cascade?
Production of fibrin clot.
What is bradykinin and its functions?
Produced from the Kinin cascade.
Causes dilation of blood vessels, acts on PGEs to stimulate nerve endings and induce pain, causes smooth muscle cell contraction, increases vascular permeability, and may increase leukocyte chemotaxis.
What are granculocytes and name them?
Primary circulating WBCs. They are neutrophils, eosinophils, and basophils.
What are scavenger receptors and where are they located?
Expressed primarily on macrophages.
They facilitate the recognition and phagocytosis of bacterial pathogens, damaged cells, altered soluble lipoproteins associated with vascular damage.
In response to stimulus, what are the biochemical mediators in the mast cell granules that are released withing seconds to exert their effects on the stimulus?
histamine, chemotactic factors, and cytokines
What are the 2 main histamine receptors and what is their function?
H1 receptors: proinflammatory, present on smooth muscle cells, especially those of the bronchi, cause bronchoconstriction when stimulated.
H2 receptors: anti-inflammatory, suppresses leukocyte fxn, abundant on parietal cells of the stomach mucosa and induces secretion of gastric acid as part of the normal physiology of the stomach.
What are the predominant leukocytes/phagocytes at work during the ealy phases of acute inflammation (within 6-12 hrs of the initial injury)?
What is the fxn of prostaglandins?
increase vascular permeability and neutrophil chemotaxis. Also induce pain.
Process by which a cell ingests and disposes of damaged cells and foreign material.
What are the 5 steps of phagocytosis?
1) opsonization, recognition of the target and adherence of the phagocyte to it.
2) engulfment (ingestsion or endocytosis) and formatio of phagosome
A deficiency in what plasma protein can result in chronic lung damage and emphysema as a result of inflammation?
After 24 hours of the initial injury, what phagocytes arrive to replace neutrophils?
Macrophages and lymphocytes
What is the primary role of the neutrophil in acute inflammatory injury?
To remove debris in sterile lesions (burns) and phagocytosis of bacteria in nonsterile lesions.
What are monocytes?
Phagocytes that are produced in the bone marrow, enter the circulation and travel to the inflammatory site where they develop into macrophages. Thus, they are the small precursor to macrophages.
What are macrophages?
Larger, more active phagocytes that are important cellular initiators of the inflammatory response. They can appear at the site within 24 hours of neutrophil infiltration. But usually arrive 3-7 days later. They are good for long defense because they can survive and divide in the acidic inflammatory site or where there is low oxygen.
What are the main differences between neutrophils and monocytes/macrophages?
1) speed (neutrophils arrive 1st)
2) active life span (macrophages survive longer)
3) chemotactic factors (not attracted by the same factors)
4) enzymatic content of their lysosomes
5) role in the immune response (macrophages are involved in activation of the "adaptive immune system", not neutrophils.)
6) role in would repair (macrophages play a larger role to initiate healing)
You have a parasitic infection. What granulocyte would you most likely find in higher amounts?
Your seasonal allergies are acting up. What granulocyte would you see most prevelant?
What is the main function of NK (natural killer) cells?
recognition and elimination of cells infected with viruses as well as cancer cells.
What biochemical messengers produced by macrophages and lymphocytes are responsible for the fever response to inflammation?
Interleukin-1: it acts on receptors of the hypothalamus to affect the body's thermostat.
You have some sort of acute infection. A CBC with differential shows an increase in "bands" or a "left shift". What is this the result of?
During acute inflammation, there is leukocytosis or an increase in circulating leukocytes (primarily neutrophils). This makes an increase in the number of immature neutrophils (bands) that migrate to the site of inflammation and show up in higher quantity on blood draws.
Your pt is ill but is a poor historian as to when the initial onset of symptoms was. You want to know if this is an acute infection or if it has been longer than about 40 hours since initial onset of inflammatory response. What lab test(s) could you order to help your determination and why?
CBC with differential - to show fibrinogen and bands: there will be increase in blood levels of fibrinogen (acute-phase reactant), and bands because of an increase in immature neutrophils migrating to the inflammatory site.
Sedementation rate - with increased fibrinogen levels comes an enhanced erythrocyte formation. The erythrocytes start to stack leading to an increased sed rate of erythrocytes.
What are the most important cells during reconstructive phase of wound healing and why?
Fibroblasts because they synthesize and secrete collagen and otehr connective tissue proteins.